This proposed research will study the degradation, reutilization and de novo synthesis of purines and purine-containing nucleic acids, nucleotides and nucleosides in the small intestine with the intention that the results from these studies will improve our understanding of the regulation of the mammalian uric acid pool. Further, results should begin to identify the sources and regulation of purine substrate for intestinal nucleotide, RNA and DNA synthesis. Therefore, these studies are relevant not only to the clinical treatment of purine-related metabolic disorders but also to problems of mucosal regeneration. Four specific aims have been identified: to evaluate I) the extent and regulation of the digestion of ribonucleic acid (RNA); II) the digestion, metabolism and transport from the lumen to the vasculature of purine nucleotides, nucleosides and bases; III) endogenous purine uptake and secretion by the small intestine; and IV) the occurrence and regulation of de novo synthesis of purines. The experiments will be conducted using perfused rat intestine, live rats and perfused live rats. Using these techniques, degradation in the lumen, transport from the lumen to the vasculature and translocation into the lumen of endogenous compounds will be studied. Radiolabeled purine compounds or precursors will be injected intralumenally or intravascularly and their metabolism and transport will be followed over time. Purine compounds will be analyzed by liquid and paper chromatography and standard scintillation counting techniques. Preliminary studies have indicated that the intestine almost quantitatively degrades dietary purines to uric acid (with the notable exception of adenine) thereby limiting the utilization of food purines for nucleotide and nucleic acid synthesis. A continuation of the preliminary studies is necessary in order to affirm and expand these findings.